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Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) remains the most investigated conjugated polymer in bioelectronics, due to its biocompatibility, high conductivity, and commercial availability. Despite these advantages, it suffers from structural and electronic instability, associated with the PSS component. Here, a graft copolymer based on ionised sulfonic modified PEDOT, poly(EDOTS-g-EDOT), was electrochemically synthesised with demonstrated structural and electronic stability and enhanced electrochemical performance. The graft copolymer was insoluble in water without crosslinking, and exhibited enhanced ion diffusion upon electrochemical switching, as revealed by its volumetric capacitance (159 ± 8 F cm-3), which was significantly higher than that of spin-coated PEDOT:PSS films (41 ± 5 F cm-3). Similarly, its performance as an active channel material in organic electrochemical transistors (OECTs) was superior to the spin-coated PEDOT:PSS, as shown for instance by its high normalised transconductance (273 ± 79 S cm-1) and a significantly high ION/IOFF ratio (19 345 ± 1205). Its short- and long-term electronic stability were also confirmed with no drop in its output drain current, despite its high swelling degree. In contrast, the spin-coated PEDOT:PSS experienced a significant deterioration in its performance over the same operational time. The facile synthesis and improved performance of poly(EDOTS-g-EDOT) highlight the importance of innovative material design in overcoming existing operational shortcomings in electronic devices.
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Organic mixed ionic-electronic conductors (OMIECs) are being explored in applications such as bioelectronics, biosensors, energy conversion and storage, and optoelectronics. OMIECs are largely composed of conjugated polymers that couple ionic and electronic transport in their structure as well as synthetic flexibility. Despite extensive research, previous studies have mainly focused on either enhancing ion conduction or enabling synthetic modification. This limited the number of OMIECs that excel in both domains. Here, a series of OMIECs based on functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) copolymers that combine efficient ion/electron transport with the versatility of post-functionalization were developed. EDOT monomers bearing sulfonic (EDOTS) and carboxylic acid (EDOTCOOH) groups were electrochemically copolymerized in different ratios on oxygen plasma-treated conductive substrates. The plasma treatment enabled the synthesis of copolymers containing high ratios of EDOTS (up to 68%), otherwise not possible with untreated substrates. This flexibility in synthesis resulted in the fabrication of copolymers with tunable properties in terms of conductivity (2-0.0019 S/cm) and ion/electron transport, for example, as revealed by their volumetric capacitances (122-11 F/cm3). The importance of the organic nature of the OMIECs that are amenable to synthetic modification was also demonstrated. EDOTCOOH was successfully post-functionalized without influencing the ionic and electronic transport of the copolymers. This opens a new way to tailor the properties of the OMIECs to specific applications, especially in the field of bioelectronics.
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Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.
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Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Rosa Bengala/farmacologia , Rosa Bengala/uso terapêutico , Oxigênio Singlete , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Cancer, a prominent cause of death, presents treatment challenges, including high dosage requirements, drug resistance, poor tumour penetration and systemic toxicity in traditional chemotherapy. Photodynamic therapy, using photosensitizers like rose bengal (RB) with a green laser, shows promise against breast cancer cells in vitro. However, the hydrophilic RB struggles to efficiently penetrate the tumour site due to the unique clinical microenvironment, aggregating around rather than entering cancer cells. In this study, we have synthesized and characterized RB-encapsulated chitosan nanoparticles with a peak particle size of ~200 nm. These nanoparticles are readily internalized by cells and, in combination with a green laser (λ = 532 nm) killed 94-98% of cultured human breast cancer cells (MCF-7) and prostate cancer cells (PC3) at a low dosage (25 µg/mL RB-nanoparticles, fluence ~126 J/cm2, and irradiance ~0.21 W/cm2). Furthermore, these nanoparticles are not toxic to cultured human normal breast cells (MCF10A), which opens an avenue for translational applications.
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Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Neoplasias da Próstata , Masculino , Humanos , Rosa Bengala/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Microambiente TumoralRESUMO
MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder resulting from the duplication of the methyl-CpG-binding protein 2 (MECP2) gene. The clinical features of MDS include severe intellectual disability, global developmental delay, seizures, recurrent respiratory infections, and gastrointestinal problems. The aim of this qualitative study was to explore how the parents of children with MDS manage their child's seizures, recurrent respiratory infections, and gastrointestinal symptoms, and the impact on them as parents. The data were coded into three categories: (1) complex care needs in the home, (2) highly skilled caregivers, and (3) impact on caregivers and families. Complex 24 h care was required and parents developed complex skillsets to ensure that this was delivered well to their child. The provision of extensive complex medical care in the home had an impact on parent mental and physical health, family dynamics, and finances. This study captures the management of high-burden comorbidities in MDS at home. Investigations into how best to support caregiver wellbeing to reduce their stresses, whilst maintaining optimal child health and wellbeing, are needed.
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BACKGROUND: To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). METHODS: Twenty-seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract-based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole-brain microstructural abnormalities in patients. RESULTS: In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p < .017). Along-the-tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false-discovery rate p < .05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p < .01). TBSS results corroborated along-tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent. CONCLUSION: DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis.
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Esclerose Lateral Amiotrófica , Encefalopatias , Substância Branca , Humanos , Imagem de Tensor de Difusão/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalopatias/patologiaRESUMO
BACKGROUND AND PURPOSE: This study sought to evaluate the relationship of progressive corticospinal tract (CST) degeneration with survival in patients with amyotrophic lateral sclerosis (ALS). METHODS: Forty-one ALS patients and 42 healthy controls were prospectively recruited from the Canadian ALS Neuroimaging Consortium. Magnetic resonance imaging scanning and clinical evaluations were performed on participants at three serial visits with 4-month intervals. Texture analysis was performed on T1-weighted magnetic resonance imaging scans and the texture feature 'autocorrelation' was quantified. Whole-brain group-level comparisons were performed between patient subgroups. Linear mixed models were used to evaluate longitudinal progression. Region-of-interest and 3D voxel-wise Cox proportional-hazards regression models were constructed for survival prediction. For all survival analyses, a second independent cohort was used for model validation. RESULTS: Autocorrelation of the bilateral CST was increased at baseline and progressively increased over time at a faster rate in ALS short survivors. Cox proportional-hazards regression analyses revealed autocorrelation of the CST as a significant predictor of survival at 5 years follow-up (hazard ratio 1.28, p = 0.005). Similarly, voxel-wise whole-brain survival analyses revealed that increased autocorrelation of the CST was associated with shorter survival. ALS patients stratified by median autocorrelation in the CST had significantly different survival times using the Kaplan-Meier curve and log-rank tests (χ2 = 7.402, p = 0.007). CONCLUSIONS: Severity of cerebral degeneration is associated with survival in ALS. CST degeneration progresses faster in subgroups of patients with shorter survival. Neuroimaging holds promise as a tool to improve patient management and facilitation of clinical trials.
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Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/patologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Canadá , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodosRESUMO
PURPOSE: Energy drinks (EDs) are not recommended for minors' consumption due to a myriad of health risks, but marketing initiatives persist. This study explored the promotion of EDs on TikTok, a platform frequented by children and adolescents. METHODS: 197 highly viewed videos from the four top ED-related hashtags on TikTok were coded for engagement variables, user information, sponsorship status, video content, and sentiment toward EDs. RESULTS: Of the 197 videos analyzed (combined 70 + million views), 29% disclosed sponsorship and 22% featured a child/adolescent. ED consumption appeared in 46% of videos, with 15% depicting hazardous consumption. Most videos (67%) had a positive sentiment toward EDs. DISCUSSION: ED-related TikTok videos are positively framed, have high engagement, and are not restricted for viewing by minors. As the platform's underage user-base grows, such videos may encourage heightened consumption. Given the known health risks, effective age-gated content restrictions are needed to reduce minors' exposure.
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Bebidas Energéticas , Mídias Sociais , Adolescente , Criança , Humanos , Vigília , Bebidas Energéticas/efeitos adversos , MarketingRESUMO
OBJECTIVE: To identify structural and neurochemical properties that underlie functional connectivity impairments of the primary motor cortex (PMC) and how these relate to clinical findings in amyotrophic lateral sclerosis (ALS). METHODS: 52 patients with ALS and 52 healthy controls, matched for age and sex, were enrolled from 5 centres across Canada for the Canadian ALS Neuroimaging Consortium study. Resting-state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy data were acquired. Functional connectivity maps, diffusion metrics and neurometabolite ratios were obtained from the analyses of the acquired multimodal data. A clinical assessment of foot tapping (frequency) was performed to examine upper motor neuron function in all participants. RESULTS: Compared with healthy controls, the primary motor cortex in ALS showed reduced functional connectivity with sensory (T=5.21), frontal (T=3.70), temporal (T=3.80), putaminal (T=4.03) and adjacent motor (T=4.60) regions. In the primary motor cortex, N-acetyl aspartate (NAA, a neuronal marker) ratios and diffusion metrics (mean, axial and radial diffusivity, fractional anisotropy (FA)) were altered. Within the ALS cohort, foot tapping frequency correlated with NAA (r=0.347) and white matter FA (r=0.537). NAA levels showed associations with disturbed functional connectivity of the motor cortex. CONCLUSION: In vivo neurochemistry may represent an effective imaging marker of impaired motor cortex functional connectivity in ALS.
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Esclerose Lateral Amiotrófica , Córtex Motor , Neuroquímica , Humanos , Imagem de Tensor de Difusão/métodos , Canadá , Imageamento por Ressonância Magnética/métodosRESUMO
The natural history of MECP2 duplication syndrome (MDS), a rare X-linked neurodevelopmental disorder with an estimated birth prevalence of 1/150,000 live births, is poorly understood due to a lack of clinical data collected for research. Such information is critical to the understanding of disease progression, therapeutic endpoints and outcome measures for clinical trials, as well as the development of therapies and orphan products. This clinical information can be systematically collected from caregivers through data collation efforts-yet, no such database has existed for MDS before now. Here, in this methodological study, we document the development, launch and management of the international MECP2 Duplication Database (MDBase). The MDBase consists of an extensive family questionnaire that collects information on general medical history, system-specific health problems, medication and hospitalisation records, developmental milestones and function, and quality of life (for individuals with MDS, and their caregivers). Launched in 2020, in its first two years of operation the MDBase has collected clinical data from 154 individuals from 26 countries-the largest sample size to date. The success of this methodology for the establishment and operation of the MDBase may provide insight and aid in the development of databases for other rare neurodevelopmental disorders.
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Since the discovery of MECP2 duplication syndrome (MDS) in 1999, efforts to characterise this disorder have been limited by a lack of large datasets, with small case series often favouring the reporting of certain conditions over others. This study is the largest to date, featuring 134 males and 20 females, ascertained from the international MECP2 Duplication Database (MDBase). We report a higher frequency of pneumonia, bronchitis, bronchiolitis, gastroesophageal reflux and slow gut motility in males compared to females. We further examine the prevalence of other medical comorbidities such as epilepsy, gastrointestinal problems, feeding difficulties, scoliosis, bone fractures, sleep apnoea, autonomic disturbance and decreased pain sensitivity. A novel feature of urinary retention is reported and requires further investigation. Further research is required to understand the developmental trajectory of this disorder and to examine the context of these medical comorbidities in a quality of life framework.
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MECP2 duplication syndrome (MDS) is a rare, X-linked, neurodevelopmental disorder caused by a duplication of the methyl-CpG-binding protein 2 (MECP2) gene-a gene in which loss-of-function mutations lead to Rett syndrome (RTT). MDS has an estimated live birth prevalence in males of 1/150,000. The key features of MDS include intellectual disability, developmental delay, hypotonia, seizures, recurrent respiratory infections, gastrointestinal problems, behavioural features of autism and dysmorphic features-although these comorbidities are not yet understood with sufficient granularity. This review has covered the past two decades of MDS case studies and series since the discovery of the disorder in 1999. After comprehensively reviewing the reported characteristics, this review has identified areas of limited knowledge that we recommend may be addressed by better phenotyping this disorder through an international data collection. This endeavour would also serve to delineate the clinical overlap between MDS and RTT.
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Deficiência Intelectual , Deficiência Intelectual Ligada ao Cromossomo X , Síndrome de Rett , Humanos , Deficiência Intelectual/genética , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Síndrome de Rett/genéticaRESUMO
Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three-dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1-weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging Consortium (CALSNIC) who underwent up to three clinical assessments and MRI at four-month intervals, up to 8 months after baseline (T0 ). Three-dimensional maps of the texture feature autocorrelation were computed from T1-weighted images. One hundred and nineteen controls and 137 ALS patients were included, with 81 controls and 84 ALS patients returning for at least one follow-up. At baseline, texture changes in ALS patients were detected in the motor cortex, corticospinal tract, insular cortex, and bilateral frontal and temporal white matter compared to controls. Longitudinal comparison of texture maps between T0 and Tmax (last follow-up visit) within ALS patients showed progressive texture alterations in the temporal white matter, insula, and internal capsule. Additionally, when compared to controls, ALS patients had greater texture changes in the frontal and temporal structures at Tmax than at T0 . In subgroup analysis, slow progressing ALS patients had greater progressive texture change in the internal capsule than the fast progressing patients. Contrastingly, fast progressing patients had greater progressive texture changes in the precentral gyrus. These findings suggest that the characteristic longitudinal gray matter pathology in ALS is the progressive involvement of frontotemporal regions rather than a worsening pathology within the motor cortex, and that phenotypic variability is associated with distinct progressive spatial pathology.
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Esclerose Lateral Amiotrófica , Substância Branca , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Canadá , Humanos , Imageamento por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
OBJECTIVE: To evaluate progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) by assessing alterations in N-acetylaspartate (NAA) ratios in the motor and prefrontal cortex within clinical subgroups of ALS. METHODS: Seventy-six patients with ALS and 59 healthy controls were enrolled in a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium. Participants underwent serial clinical evaluations and magnetic resonance spectroscopy at baseline and 4 and 8 months using a harmonized protocol across 5 centers. NAA ratios were quantified in the motor cortex and prefrontal cortex. Patients were stratified into subgroups based on disease progression rate, upper motor neuron (UMN) signs, and cognitive status. Linear mixed models were used for baseline and longitudinal comparisons of NAA metabolite ratios. RESULTS: Patients with ALS had reduced NAA ratios in the motor cortex at baseline (p < 0.001). Ratios were lower in those with more rapid disease progression and greater UMN signs (p < 0.05). A longitudinal decline in NAA ratios was observed in the motor cortex in the rapidly progressing (p < 0.01) and high UMN burden (p < 0.01) cohorts. The severity of UMN signs did not change significantly over time. NAA ratios were reduced in the prefrontal cortex only in cognitively impaired patients (p < 0.05); prefrontal cortex metabolites did not change over time. CONCLUSIONS: Progressive degeneration of the motor cortex in ALS is associated with more aggressive clinical presentations. These findings provide biological evidence of variable spatial and temporal cerebral degeneration linked to the disease heterogeneity of ALS. The use of standardized imaging protocols may have a role in clinical trials for patient selection or subgrouping. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that MRS NAA metabolite ratios of the motor cortex are associated with more rapid disease progression and greater UMN signs in patients with ALS. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02405182.
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Esclerose Lateral Amiotrófica/metabolismo , Ácido Aspártico/análogos & derivados , Disfunção Cognitiva/metabolismo , Progressão da Doença , Espectroscopia de Ressonância Magnética , Córtex Motor/metabolismo , Córtex Pré-Frontal/metabolismo , Adulto , Idoso , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/patologia , Ácido Aspártico/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Feminino , Humanos , Estudos Longitudinais , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Índice de Gravidade de DoençaRESUMO
Background: Several neuroimaging studies report structural alterations of the trigeminal nerve in trigeminal neuralgia (TN). Less attention has been paid to structural brain changes occurring in TN, even though such changes can influence the development and response to treatment of other headache and chronic pain conditions. The purpose of this study was to apply a novel neuroimaging technique-texture analysis-to identify structural brain differences between classical TN patients and healthy subjects. Methods: We prospectively recruited 14 medically refractory classical TN patients and 20 healthy subjects. 3-Tesla T1-weighted brain MRI scans were acquired in all participants. Three texture features (autocorrelation, contrast, energy) were calculated within four a priori brain regions of interest (anterior cingulate, insula, thalamus, brainstem). Voxel-wise analysis was used to identify clusters of texture difference between TN patients and healthy subjects within regions of interest (p < 0.001, cluster size >20 voxels). Median raw texture values within clusters were also compared between groups, and further used to differentiate TN patients from healthy subjects (receiver-operator characteristic curve analysis). Median raw texture values were correlated with pain severity (visual analog scale, 1-100) and illness duration. Results: Several clusters of texture difference were observed between TN patients and healthy subjects: right-sided TN patients showed reduced autocorrelation in the left brainstem, increased contrast in the left brainstem and right anterior insula, and reduced energy in right and left anterior cingulate, right midbrain, and left brainstem. Within-cluster median raw texture values also differed between TN patients and healthy subjects: TN patients could be segregated from healthy subjects using brainstem autocorrelation (p = 0.0040, AUC = 0.84, sensitivity = 89%, specificity = 70%), anterior insula contrast (p = 0.0002, AUC = 0.92, sensitivity = 78%, specificity = 100%), and anterior cingulate energy (p = 0.0004, AUC = 0.92, sensitivity = 78%, specificity = 100%). Additionally, anterior insula contrast and duration of TN were inversely correlated (p = 0.030, Spearman r = -0.73). Conclusions: Texture analysis reveals distinct brain abnormalities in TN, which relate to clinical features such as duration of illness. These findings further implicate structural brain changes in the development and maintenance of TN.
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BACKGROUND: Texture analysis (TA) is an image-analysis technique that detects complex intervoxel statistical patterns. 3D TA has shown potential in detecting cerebral degeneration not perceptible to the human eye in many neurological disorders. The reliability of this method's application in a multicenter study is unknown. PURPOSE: To assess the intrasite and intersite reliability of a novel 3D TA method from data acquired systematically from the Canadian ALS Neuroimaging Consortium (CALSNIC). STUDY TYPE: Prospective multicenter data with harmonized MR sequence parameters acquired from five sites. POPULATION: Six healthy subjects. FIELD STRENGTH: 3T 3D-MPRAGE and 3D-SPGR T1 -weighted MRI of the brain. ASSESSMENT: Voxel-based 3D TA was performed on the whole brain to produce texture maps. STATISTICAL TESTS: Intra- and intersite reliability of texture features was assessed using a two-way mixed-effects model for intraclass correlation coefficients (ICC). ICCs were calculated in a region-of-interest (ROI) analysis of predetermined anatomically relevant areas. A voxelwise approach was used to assess the whole brain. RESULTS: In the ROI analyses, intrasite reliability was excellent (ICC > 0.75) across most regions and texture features (autocorrelation [autoc], contrast [contr], energy [energ]). Intersite reliability was excellent for most regions with autoc, ranging from fair to excellent for contr, and ICCs ranging from poor to good (<0.40-0.75) for energ. Voxelwise analyses revealed a large range in ICC across the brain for both intrasite and intersite ICCs (0.0-0.90), with higher reliability in the cortical gray matter compared with deeper subcortical structures. DATA CONCLUSION: Overall, the reliability of 3D TA was highly dependent on texture feature, region studied, and method of analysis (ROI or voxelwise). Intrasite reproducibility was good to excellent, and better than intersite. ROI-based analyses present higher reliability in comparison with voxelwise analyses. Autoc has overall excellent reliability. These factors might be considered when designing future 3D TA studies. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1200-1209.
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Encéfalo , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Canadá , Humanos , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: We investigated cerebral degeneration and neurochemistry in patients with amyotrophic lateral sclerosis (ALS) using magnetic resonance spectroscopy (MRS). METHODS: We prospectively studied 65 patients and 43 age-matched healthy controls. Participants were recruited from 4 centers as part of a study in the Canadian ALS Neuroimaging Consortium. All participants underwent single-voxel proton MRS using a protocol standardized across all sites. Metabolites reflecting neuronal integrity (total N-acetyl aspartyl moieties [tNAA]) and gliosis (myo-inositol [Ino]), as well as creatine (Cr) and choline (Cho), were quantified in the midline motor cortex and midline prefrontal cortex. Comparisons were made between patients with ALS and healthy controls. Metabolites were correlated with clinical measures of upper motor neuron dysfunction, disease progression rate, and cognitive performance. RESULTS: In the motor cortex, tNAA/Cr, tNAA/Cho, and tNAA/Ino ratios were reduced in the ALS group compared with controls. Group differences in tNAA/Cr and tNAA/Cho in the prefrontal cortex displayed reduced ratios in ALS patients; however, these were not statistically significant. Reduced motor cortex ratios were associated with slower foot tapping rate, whereas only motor tNAA/Ino was associated with finger tapping rate. Disease progression rate was associated with motor tNAA/Cho. Verbal fluency, semantic fluency, and digit span forwards and backwards were associated with prefrontal tNAA/Cr. CONCLUSIONS: This study demonstrates that cerebral degeneration in ALS is more pronounced in the motor than prefrontal cortex, that multicenter MRS studies are feasible, and that motor tNAA/Ino shows promise as a potential biomarker.
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The incorporation of a hexadecyl group on imidazolium, pyridinium, and pyrrolidinium scaffolds produces low-molecular-weight ionic organogelators that can gel several types of ionic liquids, deep eutectic solvents (DESs), and several molecular organic solvents. Minimum gelator concentrations fall in the 0.9-15.0% (w/v) range, with the lower end of the gelator concentrations observed in the gelation of DESs. On the basis of polarized optical microscopy, differential scanning calorimetry, and X-ray data, crystallization of these salts appear to produce high-surface-area crystals, which generate sufficiently stable three-dimensional networks that are capable of trapping the solvent molecules. Importantly, the nature of the fluid component of the gel appears to have a profound effect on the morphology of the crystallized organogelators. On the other hand, the organogelators appeared to modulate phase transitions of the liquids.
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Photochemical tissue bonding with chitosan-based adhesive films is an experimental surgical technique that avoids the risk of thermal tissue injuries and the use of sutures to maintain strong tissue connection. This technique is advantageous over other tissue repair methods as it is minimally invasive and does not require mixing of multiple components before or during application. To expand the capability of the film to beyond just a tissue bonding device and promote tissue regeneration, in this study, we designed bioadhesive films that could also support stem cells. The films were modified with oligomeric chitosan to tune their erodibility and made porous through freeze-drying for better tissue integration. Of note, porous adhesive films (pore diameter â¼110 µm), with 10% of the chitosan being oligomeric, could retain similar tissue bonding strengths (13-15 kPa) to that of the nonporous chitosan-based adhesives used in previous studies when photoactivated. When tested in vitro, these films exhibited a mass loss of â¼20% after 7 days, swelling ratios of â¼270-300%, a percentage elongation of â¼90%, and both a tensile strength and Young's modulus of â¼1 MPa. The physical properties of the films were suitable for maintaining the viability and multipotency of bone-marrow-derived human mesenchymal stem cells over the duration of culture. Thus, these biocompatible, photoactivated porous, and erodible adhesive films show promise for applications in controlled cell delivery and regenerative medicine.
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Quitosana/farmacologia , Células-Tronco Mesenquimais/citologia , Cicatrização/efeitos dos fármacos , Animais , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Módulo de Elasticidade , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanoporos/ultraestrutura , Porosidade , Ovinos , Suturas , Resistência à Tração , Adesivos Teciduais/farmacologiaRESUMO
AIM: The aim of this study was to assess the incidence and prevalence of MECP2 duplication syndrome in Australian children and further define its phenotype. METHODS: The Australian Paediatric Surveillance Unit was used to identify children with MECP2 duplication syndrome between June 2014 and November 2017. Reporting clinicians were invited to complete a questionnaire. Clinician data (n = 20) were supplemented with information from the International Rett Syndrome Phenotype Database and from caregivers (n = 7). Birth prevalence and diagnostic incidence were calculated. RESULTS: The birth prevalence of MECP2 duplication syndrome in Australia was 0.65/100 000 for all live births and 1/100 000 for males. Diagnostic incidence was 0.07/100 000 person-years overall and 0.12/100 000 person-years for males. The median age at diagnosis was 23.5 months (range 0 months-13 years). A history of pneumonia was documented in three quarters of the clinical cases, half of whom had more than nine episodes. Cardiovascular abnormalities were reported in three cases. A clinical vignette is presented for one child who died due to severe idiopathic pulmonary hypertension. The majority (13/15) of males had inherited the duplication from their mothers, and two had an unbalanced translocation. CONCLUSIONS: MECP2 duplication syndrome is a rare but important diagnosis in children because of the burden of respiratory illness and recurrence risk. Pulmonary hypertension is a rare life-threatening complication. Array comparative genomic hybridisation testing is recommended for children with undiagnosed intellectual disability or global developmental delay. Early cardiac assessment and ongoing monitoring is recommended for MECP2 duplication syndrome.